Influenza is an acute infectious disease in man caused by one of three types of influenza viruses. Once introduced into a susceptible community, the disease spreads rapidly from person to person by droplet transmission. Although of low mortality, influenza is marked by a high rate of morbidity.
Treatement of influenza is essentially palliative and symptomatic in nature. Sulfonamides, antibiotics and chemical agents have little, if any, effect in the treatment of this disease. Some use has been made in treating influenza with animal-immune serum or human convalescent serum, but in general, prophylactic immunization to produce a vaccine-induced immunity is the only measure readily available for the prevention of this disease.
Immunization using live viruses has received some consideration in the prevention of this disease. As a practical matter, however, such immunization has not proven effective due to the simultaneous circulation of numerous strains of influenza, each strain having its own serological and immunological characteristics. Thus, it is highly speculative to attenuate a particular strain of influenza and prepare a live virus vaccine therefrom, only to subsequently find another influenza strain to be the prevalent strain. Accordingly, immunization using a killed or inactivated virus vaccine prepared from the currently prevalent influenza strain is the most effective method known in preventing this disease.
Prior to the present invention, killed or inactivated influenza vaccines, particularly those containing type B antigen, had acquired a well-deserved reputation for producing certain undesirable side-effects. Various reasons for these reactions have been attributed to such factors as the inherent toxicity of the virus itself, allergic reactions to viral antigens prepared from egg protein used in the preparation of such vaccines, and the presence of impurities in the vaccine. This problem of vaccine toxicity has assumed even more importance in recent years, inasmuch as the amount of type B anitgen required in standard influenza vaccines has been steadily increasing. Thus, in 1972, the amount of type A anigent was increased from 400 to 700 CCA units in standard bivalent vaccines available with no appearent increase in the reactongenicity of the vaccine, (CCA refers to Chick Cell Agglutination activity per unit weight of protein nitrogen, Miller, G. L. and Stanley, W. M., J. Exp. Med. 79, 185-95, 1944). Two years later, however, when the amount of type B antigen was increased from 300 to 500 CCA units, numerous reports of patients experiencing local and systemic reactions ensued. Accordingly, numerous investigators have sought to minimize these undesirable reactions due to the increased amounts of type B antigen currently being administered.
Following a long series of investigations, applicants have discovered a relatively simple procedure for the detoxification of influenza type B antigen, which results in the elimination of much of the undesirable type B antigen reactongenicity associated with the administration of increased amounts of type B antigen. In short, treatment of an inactivated type B influenza virus with relatively high concentrations of formaldehyde for an extended period of time enables the preparation of an inactivated, detoxified type B vaccine having a reduced reactogenicity. The detoxification process described herein is readily adapted to large scale vaccine production, and is remarkably effective in eliminating to a large extent the untoward side-effects obtained with type B antigen. At the same time, this detoxification process, when practiced in accordance with the teachings of this invention, does not comprise the antigenicity or the effectiveness of either monovalent or bivalent vaccines containing type B antigen.